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Genetic factors responsible for hereditary breast and ovarian cancer development Large rearrangements in BRCA1 and BRCA2 genes
Tichá, Ivana
Background: A greatly increased risk for development of hereditary breast cancer is associated with germline mutations in several susceptibility genes. In this study we analyzed large genomic rearrangements (LGRs) in BRCA1/2 genes and we also focused on the role of CHEK2 and TP53 in tumorigenesis. Methods: A series of 586 high risk patients with breast/ovarian cancer that had previously been tested negatively for small mutations in BRCA1/2 was screened for LGRs by MLPA, LR-PCR and sequencing. Chromosome 17-specific aCGH was used to locate deletion breakpoints in regions flanking the BRCA1 gene. MLPA-analysis was also used to detect two frequently occurring mutations in CHEK2 (c.1100delC and a deletion of 5395 bp). The coding region of the TP53 gene was analyzed by sequencing. Results: We identified 9 different LGRs in the BRCA1 gene in 16 patients. Five alterations (deletion of exons 1-17, 5-10, 13-19, 18-22 and 21-24) were novel. Deletions of exons 1-17, 5-14 and 21-22 were identified repeatedly, and represented population specific (founder) mutations. LGRs accounted for 12.1% (16/132) of all detected pathogenic BRCA1 mutations. No LGRs were found in the BRCA2 gene. Pathogenic mutations in other tested genes were less frequent; 2 were detected in TP53 and 9 in CHEK2. Conclusions: In our population, LGRs...
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Inactivation of tumor suppressor genes contributing to pathogenesis of sporadic cancers.
Zdařilová, Klára ; Janatová, Markéta (advisor) ; Tichá, Ivana (referee)
Protein product tumor suppressor PALB2 gene plays a major role in pathway of DNA repair of double-strand breaks throught the homologous recombination mechanism. Significance of its pathogenic variants in hereditary forms of breast cancer in BRCA1/2- negative patients in families with multiple breast cancers may be in the Czech Republic comparable with the BRCA2 gene. A role of the PALB2 gene in sporadic breast cancer occurence, which represent 90 - 95 % of all cancers, is still unknown. This thesis focuses on inactivation pathway of tumor suppressor PALB2 in the sporadic breast cancer by a mechanism of allelic loss detecting by loss of heterozygosity (LOH) of corresponding microsatellite markers and hypermethylation of promoter region as the most common mechanisms of inactivation tumor suppressors in early tumorigenesis. In a group of 51 nonselected patients with sporadic breast cancer we found four samples with PALB2 locus allelic loss. These samples were analyzed for somatic mutations. No mutation was found. There is no evidence of promotor hypermethylation in any of the samples. Our data suggest a role of the PALB2 gene inactivation in a minority group of sporadic breast cancers.
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Genetic factors responsible for hereditary breast and ovarian cancer development Large rearrangements in BRCA1 and BRCA2 genes
Tichá, Ivana
Background: A greatly increased risk for development of hereditary breast cancer is associated with germline mutations in several susceptibility genes. In this study we analyzed large genomic rearrangements (LGRs) in BRCA1/2 genes and we also focused on the role of CHEK2 and TP53 in tumorigenesis. Methods: A series of 586 high risk patients with breast/ovarian cancer that had previously been tested negatively for small mutations in BRCA1/2 was screened for LGRs by MLPA, LR-PCR and sequencing. Chromosome 17-specific aCGH was used to locate deletion breakpoints in regions flanking the BRCA1 gene. MLPA-analysis was also used to detect two frequently occurring mutations in CHEK2 (c.1100delC and a deletion of 5395 bp). The coding region of the TP53 gene was analyzed by sequencing. Results: We identified 9 different LGRs in the BRCA1 gene in 16 patients. Five alterations (deletion of exons 1-17, 5-10, 13-19, 18-22 and 21-24) were novel. Deletions of exons 1-17, 5-14 and 21-22 were identified repeatedly, and represented population specific (founder) mutations. LGRs accounted for 12.1% (16/132) of all detected pathogenic BRCA1 mutations. No LGRs were found in the BRCA2 gene. Pathogenic mutations in other tested genes were less frequent; 2 were detected in TP53 and 9 in CHEK2. Conclusions: In our population, LGRs...
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Genetic factors responsible for hereditary breast and ovarian cancer development Large rearrangements in BRCA1 and BRCA2 genes
Tichá, Ivana ; Pohlreich, Petr (advisor) ; Souček, Pavel (referee) ; Stiborová, Marie (referee)
2. Summary Background: A greatly increased risk for development of hereditary breast cancer is associated with germline mutations in several susceptibility genes. In this study we analyzed large genomic rearrangements (LGRs) in BRCA1/2 genes and we also focused on the role of CHEK2 and TP53 in tumorigenesis. Methods: A series of 586 high risk patients with breast/ovarian cancer that had previously been tested negatively for small mutations in BRCA1/2 was screened for LGRs by MLPA, LR-PCR and sequencing. Chromosome 17-specific aCGH was used to locate deletion breakpoints in regions flanking the BRCA1 gene. MLPA-analysis was also used to detect two frequently occurring mutations in CHEK2 (c.1100delC and a deletion of 5395 bp). The coding region of the TP53 gene was analyzed by sequencing. Results: We identified 9 different LGRs in the BRCA1 gene in 16 patients. Five alterations (deletion of exons 1-17, 5-10, 13-19, 18-22 and 21-24) were novel. Deletions of exons 1-17, 5-14 and 21-22 were identified repeatedly, and represented population specific (founder) mutations. LGRs accounted for 12.1% (16/132) of all detected pathogenic BRCA1 mutations. No LGRs were found in the BRCA2 gene. Pathogenic mutations in other tested genes were less frequent; 2 were detected in TP53 and 9 in CHEK2. Conclusions: In our...
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Competitive advantage
Marešová, Anežka ; Tichá, Ivana (advisor) ; Jiří , Jiří (referee)
The thesis deals with the competitiv eadvantage of the company PROGRAMM s.r.o. The theoretical part containsthe basic terms such as competitive advantage, competitiveness, strategy and more. Furthermore, itcontainscompetitor analysis, situation alanalysis, analysis of internal and external environment, marketing mix and SWOT analysis.
The practical part contains the situation alanalysis of the company PROGRAMM s.r.o. including analysis of the internal environment, marketing mix of the company and the analysis of external environment. Furthermore, the marketing research and analysis of the biggest competitor, the company KVADOS, a.s. has been done. Theresults are summed up with a SWOT analysis and the competitive advantages of the company PROGRAMM s.r.o. are defined. The weaknesses of the company are defined and possiblesolutions are suggestedprimarilyfocused on marketing in order to gainanotheradvantages and benefit from them.
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Manager Remuneration
Hebelka, Petr ; Tichá, Ivana (advisor) ; Pavel, Pavel (referee)
The diploma thesis is manager remuneration in non-profit organization which is called Technické služby Hradec Králové. The system of remuneration must be simple and fair. The theoretical part is focused on remuneration relating to government. The practical part is focused on mentioned non-profit organization and it suggests the systematical solution of manager remuneration of each center based on budget implementation. At the end of the diploma is evaluated a benefit for readers and author.
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Business process improvement
Brádlová, Zdena ; Tichá, Ivana (advisor) ; Lucie, Lucie (referee)
The present master´s thesis deals with the topic of improving company processes. Within the framework of environmental management it focuses on the topic of company waste management. The goal of the thesis is to perform assessment of the waste management and to formulate recommendations. Theoretical part of the thesis provides interpretation of terms related to the process, process management and environmental management, focusing primarily on the area of waste management. Practical part then pursues to provide information on waste management process and to identify factors influencing the process. Final part comprises recommendations for the company management.
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Opportunities for human capital development
Morgensternová, Erika ; Tichá, Ivana (advisor) ; Fajčíková, Adéla (referee)
Summary
Bachelor thesis is focused on the theme of human capital and its possibilities for development. The aim is to assess the current level of human capital in a selected company, which for these purposes has become an engineering company, and identify the degree of motivation for its development. The theoretical part of his introduction discusses the history of the development of the issue and then the whole issue was explored deeper in terms of development opportunities, level of motivation, education or investments and costs in human capital. In the analytical part they were applied their theoretical knowledge. In selected engineering firm was carried out a survey on a selected group of respondents among blue-collar occupations, whose purpose was to obtain sufficient information to assess the level of human capital and then suggest possible solutions to promote motivation to develop human capital by employers.
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Economical impact of human capital Development in the Compan
Janurová, Michaela ; Tichá, Ivana (advisor) ; Pavel, Pavel (referee)
This thesis titled Economic impacts of human resource development is focused on the assessment of particular system, which is used in the context of human resource management to iprove working efficienci. The theoretical part is focused on the specification of human resource management, appearance and development. Generally, reference is made to performance management, motivation and stimulation of employees. I analyzed the methods of remuneration, performance evaluation and employee skills. In the partical part the particular company and applied human resources management system, a system of performance appraisal, employee skills and education. Part of this chapter is focused on a group of executives of the company. The findings are evaluated and designed a more appropriate way of motivating and rewarding. Finally, possibilities are summarized and recommendet for efficient improvments to existing system in society.
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